Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis

Steiner A Z, Terplan M, Paulson R J

CRD summary

This review compared the effectiveness of tamoxifen and clomiphene in terms of ovulation induction and pregnancy rates. The authors concluded that there are no substantial differences in ovulation rates between tamoxifen and clomiphene, while limited data show no significant differences in pregnancy rates or outcomes. This was generally a well-conducted review and the authors' conclusions are likely to be reliable.

Authors' objectives

To compare the effectiveness of tamoxifen and clomiphene in terms of ovulation induction and pregnancy rates.

Searching

MEDLINE (1966 to January 2005), PREMEDLINE, CINAHL, International Pharmaceutical Abstracts, the Cochrane Database of Systematic Reviews, ACP Journal Club, DARE, the Cochrane Controlled Trials Register and BIOSIS Previews (all to January 2005) were searched without language restrictions using the reported search terms. Experts in the field provided papers from personal files. The reference lists in identified studies and reviews were also screened.

Study selection

Study designs of evaluations included in the review

Prospective clinical trials (including crossover studies) were eligible for inclusion. Abstracts were included only where additional information could be obtained from the authors. All of the included studies were randomised controlled trials (RCTs).

Specific interventions included in the review

Studies that compared tamoxifen with clomiphene for the induction of ovulation were eligible for inclusion. In the included studies, tamoxifen was administered in doses ranging from 20 to 80 mg per treatment day of cycle and clomiphene in doses ranging from 25 to 200 mg per treatment day of cycle (full details of treatment cycles were reported).

Participants included in the review

Studies of infertile couples with isolated anovulatory infertility were eligible for inclusion if they enrolled oligo-ovulatory or anovulatory women with no known tubal disease and partners with normal semen analysis.

Outcomes assessed in the review

The primary review outcomes were ovulation and pregnancy per cycle. The review also assessed the live-birth rate.

How were decisions on the relevance of primary studies made?

Three reviewers performed the initial screening of titles and abstracts, and two reviewers independently selected studies. Any disagreements were resolved by consensus.

Assessment of study quality

The authors did not report a formal validity assessment process, although data on the methods of treatment allocation, allocation concealment, blinding and reporting of a power calculation were briefly summarised. Two reviewers independently assessed study design and resolved any disagreements by consensus.

Data extraction

Two reviewers independently extracted the data and resolved any disagreements by consensus. For each study, the number of events of interest per cycle was extracted for all cycles.

Methods of synthesis

How were the studies combined?

Pooled odds ratios (ORs) with 95% confidence interval (CIs) were calculated using the random-effects model of DerSimonian and Laird. The potential for publication bias was tested using Begg's test (P<0.1 indicated statistical significance).

There were no substantial differences in ovulation rates between tamoxifen and clomiphene. Limited data on pregnancy rates and outcomes showed no significant differences between the treatments.

CRD commentary

The review addressed a clear question that was defined in terms of the participants, intervention, outcomes and study design. Several relevant sources were searched and attempts were made to minimise publication and language bias; appropriate methods were used to assess the presence of publication bias, and no evidence of it was found. Methods were used to minimise reviewer errors and bias in the review process. Statistical heterogeneity was assessed and the studies were appropriately pooled in a meta-analysis. The authors calculated the power of the meta-analysis to detect a treatment difference, which adds support to the finding of no difference between treatments. This was a generally well-conducted review and the authors' conclusions are likely to be reliable.

Implications of the review for practice and research

Practice: The authors stated that clinicians may choose whichever regimen they are familiar with.

Research: The authors stated that there is a need for further studies to compare tamoxifen with clomiphene in clinical settings. They also stated that further studies are required to assess and compare the effects of tamoxifen and clomiphene in women with polycystic ovarian syndrome or obesity.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.